A Molecular Dynamics Examination on Mutation-Induced Catalase Activity in Coral Allene Oxide Synthase
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- 作者：Phil De Luna ; Eric A. C. Bushnell ; James W. Gauld
- 刊名：Journal of Physical Chemistry B
- 出版年：2013
- 出版时间：November 27, 2013
- 年：2013
- 卷：117
- 期：47
- 页码：14635-14641
- 全文大小：357K
- 年卷期：v.117,no.47(November 27, 2013)
- ISSN：1520-5207
文摘
Coral allene oxide synthase (cAOS) catalyzes the formation of allene oxides from fatty acid hydroperoxides. Interestingly, its active site differs from that of catalase by only a single residue yet is incapable of catalase activity. That is, it is unable to catalyze the decomposition of hydrogen peroxide to molecular oxygen and water. However, the single active-site mutation T66V allows cAOS to exhibit catalase activity. We have performed a series of molecular dynamics (MD) simulations in order to gain insights into the differences in substrate (8R-hydroperoxyeicosatetraenoic) and H2O2 active site binding between wild-type cAOS and the T66V mutant cAOS. It is observed that in wild-type cAOS the active site Thr66 residue consistently forms a strong hydrogen-bonding interaction with H2O2 (catalase substrate) and, importantly, with the aid of His67 helps to pull H2O2 away from the heme Fe center. In contrast, in the T66V-cAOS mutant the H2O2 is much closer to the heme鈥檚 Fe center and now forms a consistent Fe路路路O2H2 interaction. In addition, the His67路路路H2O2 distance shortens considerably, increasing the likelihood of a Cpd I intermediate and hence exhibiting catalase activity.